title: Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients.
abstract: We previously identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88, recognized by CD8+ cytotoxic T lymphocytes (CTL). Subsequently, we attempted clinical trials with this epitope peptide alone for some malignancies, resulting in clinical and immunological responses, although their potential was not strong enough for routine clinical use as a cancer vaccine. In the current study, to assess whether immunogenicity of the survivin-2B80-88 peptide could be enhanced with other vaccination protocols, we performed clinical trials in advanced colon cancer patients with two vaccination protocols: (i) survivin-2B80-88 plus incomplete Freund's adjuvant (IFA); and (ii) survivin-2B80-88 plus IFA and a type-I interferon (IFN), IFNα. Our data clearly indicated that, although the effect of survivin-2B80-88 plus IFA was not significantly different from that with survivin-2B80-88 alone, treatment with the vaccination protocol of survivin-2B80-88 plus IFA and IFNα resulted in clinical improvement and enhanced immunological responses of patients. Tetramer analysis of survivin-2B80-88 peptide-specific CTL demonstrated that such CTL were increased at least twofold after vaccination with this protocol in four of eight patients. In these patients, enzyme-linked immunosorbent spot (ELISPOT) results were also enhanced. Subsequent study of single-cell clone separation by cell sorting of peptide-specific CTL showed that each CTL clone was indeed not only peptide-specific but also cytotoxic against human cancer cells in the context of the expression of both HLA-A24 and survivin molecules. Taken together, these results indicate that vaccination of colon cancer patients with survivin-2B80-88 plus IFA and IFNα can be considered to be a very potent immunotherapeutic regimen, and that this protocol might work for other cancers.
authors.affiliation: Departments of Surgery Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kameshima
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tsuruma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Akari
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Shingo
authors.initials: S
authors.lastname: Ichimiya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000008:administration & dosage / Q000276:immunology*; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D051034:Inhibitor of Apoptosis Proteins; D007370:Interferon Type I; D010446:Peptide Fragments; D000077022:Survivin